While they potentially offer many advantages due to their “organic nature,” conventional poly(α-amino acids) possess many undesirable physical, chemical and biodegradation properties. For example, the biological and material properties of conventional poly(α-amino acids) cannot be varied over a wide range. In addition, the synthesis of many conventional poly(α-amino acids) is difficult and expensive.
A considerable amount of attention has therefore been focused on replacing the amide (peptide) linkage in the conventional poly(α-amino acids) with a variety of non-amide bonds to provide novel polymeric systems that are based on α-amino acids. One class of α-amino acid derived polymers are polyisopeptides (alternatively known as pseudo-poly(amino acids)), which belong to the XY-type heterochain polymers. Polyisopeptides are usually formed by linking trifunctional α-amino acids in the backbone chains. However, relatively few attempts have been made to synthesize polyisopeptides. For example, Sekiguchi et al. obtained poly-β-(α-alkyl-L-aspartate) by the ring-opening polymerization of β-lactams. See, Rodriguez-Galan, A. et al., Makromol. Chem., Macromol. Symp., 6, 277 (1986) and Vives, J. et al., Makromol. Chem., Rapid Commun., 10(1):13 (1989). One major limiting feature of polyisopeptides is that structural modifications are limited solely to chemical variations at the N-acyl residue of the polyisopeptide. This narrow range of chemical modification has resulted in an undesirably narrow range of material properties of these polymers.
Another class of α-amino acid derived polymers are amino acid based bioanalagous polymers (AABBPs), which belong to the XX-YY heterochain polymers. AABBPs are mainly obtained by the polycondensation of XX (one type of monomer having two X functional groups) and YY (another type of monomer having two Y functional groups). AABBPs are not pure polyamino acids or pseudo-polyamino acids because they include residues of other types of monomers (e.g., dicarboxylic acids and diols).
One class of AABBPs are poly(ester ureas) (PEUs), which are prepared from bis-α-aminoacyl diol monomers. The first attempt to use bis-α-aminoacyl(phenylalanyl) diol for preparing bioabsorbable, semi-physiological polymers similar to poly(ester urea) was by Huang et al. Huang S. J., et al., J. Appl. Polym. Sci., 23(2): 429 (1979). Only low-molecular-weight PEUs, having limited material properties, could be prepared by this route.
Lipatova et al. have also synthesized semi-physiological poly(ester urethane ureas) from bis-L-phenylalanyl diols, diols, and diisocyanates. Lipatova T. E., et al., Dokl. Akad. Nauk SSSR, 251(2): 368 (1980) and Gladyr I. I., et al. Vysokomol. Soed., 31B(3): 196 (1989). However, no information on the synthesis of the starting material (e.g., α-diamino diesters) was given.
Yoneyama et al. reported on the synthesis of high-molecular-weight semi-physiological PEUs by the interaction of free α-diamino-diesters with non-physiological diisocyanates. Yoneyama M., et al., Polym. Prepr. Jpn., 43(1): 177 (1994). Contrary to Huang et al. (Huang S. J., et al., J. Appl. Polym. Sci., 23(2): 429 (1979)), high-molecular-weight PEUs were obtained in some cases. In view of this preliminary data, there remains an ongoing need for novel polymers based on α-amino acids that possess a wide range of physical, chemical and biodegradation properties.